Treatment of rats and guinea pigs with reserpine causes an increase in the accumulation of cyclic AMP in chopped cerebral cortex incubated in vitro with adenosine. It is proposed to study the mechanism of this effect by manipulating the endogenous neuromodulators by conventional synthesis inhibitors or specific neuronotoxic agents. Psychotropic drugs cause increases in the cyclic AMP content of this tissue in vitro. The inclusion of theophylline prevents most or all of this increase. Drugs showing this effect include the tricyclic antidepressants and some neuroleptic drugs. This data suggests that the effect of the drugs is mediated by causing the release and action of adenosine. The proposed work will attempt to demonstrate this in the chopped tissue and also in a frozen mouse model by direct assay of adenosine. The results may be relevant to the clinical effects or toxic effects of these drugs as the doses of many of these drugs might approach the high concentrations of drug used in this study, 10 to the minus 4th power M.